Abstract
Solid tumors require the formation of a vascular network derived from host blood vessels to support their growth. The heparin-binding growth factor family was the first class of angiogenesis factors to be studied. These proteins play key roles in a variety of crucial biological activities that require cell growth, differentiation, migration and chemotaxis. Our work presents the study of a group of polyanionic compounds, the naphthalene sulfonic distamycin A derivatives, named suradistas, which represents a new class of inhibitors of neo-angiogenesis that can counteract vascularization of solid tumors. By a combination of in vitro and in vivo approaches, a leader compound, PNU145156E, was selected. The results suggest that PNU145156E interacts directly with the heparin-binding growth factor bFGF in a specific manner. It forms a tight but reversible 1 to 1 complex with the protein, inducing conformational changes, which render bFGF less stable, preventing the interaction with heparin and the biologically effective dimerization of the growth factor.
Original language | English |
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Pages (from-to) | 23-35 |
Number of pages | 13 |
Journal | Journal of Molecular Structure |
Volume | 792-793 |
DOIs | |
Publication status | Published - Jul 3 2006 |
Keywords
- Angiogenesis
- bFGF
- Cancer
- Fluorescence spectroscopy
- Heparin-binding growth factors
- Naphthalene sulfonic distamycin A derivatives
- Suradista
ASJC Scopus subject areas
- Structural Biology
- Organic Chemistry
- Physical and Theoretical Chemistry
- Spectroscopy
- Atomic and Molecular Physics, and Optics
- Materials Science (miscellaneous)